Recombinant adenovirus (rAd) vectors have desirable features for gene delivery, including wide tissue and cell tropism, the capacity to accommodate large expression cassettes and high transduction efficiency, and the capability to infect resting cells. The extremely row integrational tendency of adenoviruses is favourable as an additional safety aspect, since it minimizes the risk of insertion mutagenesis and oncogenic activation. A large number of different serotypes of human adenoviruses also provide choice of various viral sheaths with very different tropism. For example, group C viruses are extremely infectious for the liver or muscles, group D for cells of the central nervous system or group B for cells of the hemopoetic system. In addition, adenovirus is well suited for pharmaceutical development as the virus grows to high specific titers and scalable manufacturing processes have been established (Huyghe et al., 1995a; Shabram et al., 1997a).
Despite these decisive advantages the application possibilities for adenovirus vectors still remain limited. This is due to the fact that the adenoviruses vectors contain viral genes that are expressed in the target tissue. Direct toxicity, cut-off expression, inflammation of the tissue (Simon et al., 1993) and attack of cytotoxic T-lyphocytes are results which finally lead to destruction of infected cells. Numerous groups have tried to reduce the immunogenity of adenoviral vectors. E2 and E4 regions, which also have a transactivating function, where eliminated from the virus genome and were transferred into the helper cell line. However, it remains uncertain, whether these changes, which additionally cause reduction of the virus titres, are able to augment the duration of expression in vivo. As consequential continuation of this concept adenovirus vectors were developed in recent years, which are free from viral genes (Hardy et al., 1997; Kochanek et al., 1996; Kumar-Singh and Chamberlain, 1996; Mitani et al., 1995; Parks et al., 1996). However, such vectors are of little use for large scale pharmaceutical production.